Oral delivery of Sunitinib malate using carboxymethyl cellulose/poly(acrylic acid-itaconic acid)/Cloisite 30B nanocomposite hydrogel as a pH-responsive carrier.

This work aimed to fabricate a Cloisite 30B-incorporated carboxymethyl cellulose graft copolymer of acrylic acid and itaconic acid hydrogel (Hyd) via a free radical polymerization method for controlled release of Sunitinib malate anticancer drug. The synthesized samples were characterized by FTIR, XRD, TEM, and SEM-dot mapping analyses. The encapsulation efficiency of Hyd and Hyd/Cloisite 30B (6 wt%) was 81 and 93%, respectively, showing the effectiveness of Cloisite 30B in drug loading. An in vitro drug release study showed that drug release from all samples in a buffer solution with pH 7.4 was higher than in a buffer solution with pH 5.5. During 240 min, the cumulative drug release from Hyd/Cloisite 30B (94.97% at pH 7.4) is lower than Hyd (53.71% at pH 7.4). Also, drug-loaded Hyd/Cloisite 30B (6 wt%) demonstrated better antibacterial activity towards S. Aureus bacteria and E. Coli. High anticancer activity of Hyd/Cloisite 30B against MCF-7 human breast cancer cells was shown by the MTT assay, with a MCF-7 cell viability of 23.82 ± 1.23% after 72-hour incubation. Our results suggest that Hyd/Cloisite 30B could be used as a pH-controlled carrier to deliver anticancer Sunitinib malate.

Model-based investigation of the pH-dependent chromatographic separation of itaconic acid from aqueous solution using strongly hydrophobic adsorbents.

In this study, we propose a model for the simulation of the pH-dependent separation of dicarboxylic acids from aqueous solutions using strongly hydrophobic adsorbents. Building upon results of our previous study, where we experimentally investigated the pH-dependent adsorption behavior of the individual acid species of itaconic acid (IA) on a strongly hydrophobic adsorbent using in-line Raman spectroscopy, we utilize a transport-dispersive model as the basis for our simulation model. Instead of considering IA as a single component in our model, we simulated each acid species of IA individually. For this purpose, we expanded the transport-dispersive model with reaction terms in all aqueous phases. The reaction terms include all dissociation reactions of all involved components for each time step and spatial discretization. This model enables the time and spatial dependent simulation of the pH value in the chromatographic column and thus the time and spatial dependent knowledge of each acid species concentration. The consideration of activity coefficients due to high local ionic strength is achieved using the Truesdell-Jones (TdJ) model. The simulation model is successfully validated using experimental data from our previous study and used in a simulation study that demonstrates the potential of the model approach for analyzing associated separation tasks.

Pickering emulsion of pepper essential oil stabilized by Octenyl succinic acid starch: Characterization, in vitro release and anticancer activity.

Under high humidity and high temperature conditions, the quality of pepper essential oil easily deteriorates, and the oxidation of oil restricts its application, especially for the insolubility in water. This study investigated pepper essential oil encapsulated in Pickering emulsion with octenyl succinic acid starch, which was effectively able to reduce 100 times of the release rate. The smooth surface and complete particles of the emulsion were observed and no new chemical bonds were formed. The minimum particle sizes were 2.05 µm and 1.89 µm, when the Pickering emulsion was set to different storage conditions at pH 5 and 0.1 M NaCl, respectively. During gastrointestinal digestion, the release of essential oils was effectively delayed in the Pickering emulsion and the digestibility of the emulsion was 16.93% in 120 min. Compared with untreated cells, Pickering emulsion can effectively inhibit the proliferation of MCF-7 (52.71%). All these results indicate that OSA starch stabilized pepper essential oil can effectively increase solubility, improve stability, and expand the application range. Therefore, it can provide a theoretical basis for applications of pepper essential oil, especially for the functional drug application.

Octenylsuccinylation strategy to construct high-amylose maize starch-myristic acid complexes with high thermal stability, complexation efficiency and anti-retrogradation ability.

Gelatinizing high-amylose maize starch (HAMSt) requires high temperatures to allow complexation with lipids, making it a challenging process. An octenylsuccinylation method was examined as a part of a strategy to decrease the gelatinization temperature of HAMSt, thereby promoting the complexation between HAMSt and myristic acid (MAc). Octenyl succinic anhydride (OSA) modification of HAMSt reduces the onset gelatinization temperature of HAMSt from 71.63 °C to 66.97 °C. Moreover, as the OSA concentration increased from 2 % to 11 %, the degree of substitution and molecular weights of the esterified HAMSt gradually increased from 0.0069 to 0.0184 and from 0.97 × 106 to 1.17 × 106 g/mol, respectively. Fourier transform infrared analysis indicated that the octenyl-succinate groups were grafted onto the HAMSt chains. The formation of HAMSt-MAc complexes improved the thermal stability of OSA-treated HAMSt (peak temperature increased by 0.11 °C-13.95 °C). Moreover, the diffraction intensity of the V-type peak of the 11 % sample was greater than that of other samples. Finally, the anti-retrogradation ability was in the order of OSA-HAMSt-MAc complexes > HAMSt-MAc complexes > HAMSt. Overall, our results indicate that octenylsuccinylation can be an effective strategy to promote the formation of OSA-HAMSt-MAc complexes and delay starch retrogradation.

Fabrication of injectable alginate hydrogels with sustained release of 4-octyl itaconate for articular anti-inflammatory.

BACKGROUND: Osteoarthritis (OA) is a chronic and degenerative joint disease that remains a great challenge in treatment due to the lack of effective therapies. 4-octyl itaconate (4-OI) is a novel and potent modulator of inflammation for the treatment of inflammatory disease. However, the clinical usage of 4-OI is limited due to its poor solubility and low bioavailability. As a promising drug delivery strategy, injectable hydrogels offers an effective approach to address these limitations of 4-OI. OBJECTIVE: The aim of the study was to verify that the composite 4-OI/SA hydrogels could achieve a controlled release of 4-OI and reduce damage to articular cartilage in the group of osteoarthritic rats treated with the system. METHODS: In this study, an injectable composite hydrogel containing sodium alginate (SA) and 4-octyl itaconate (4-OI) has been developed for continuous intra-articular administration in the treatment of OA. RESULTS: After intra-articular injection in arthritic rats, the as-prepared 4-OI/SA hydrogel containing of 62.5 µM 4-OI effectively significantly reduced the expression of TNF-α, IL-1ß, IL-6 and MMP3 in the ankle fluid. Most importantly, the as-prepared 4-OI/SA hydrogel system restored the morphological parameters of the ankle joints close to normal. CONCLUSION: 4-OI/SA hydrogel shows a good anti-inflammatory activity and reverse cartilage disruption, which provide a new strategy for the clinical treatment of OA.

Injectable Hydrogel of Chitosan-Octyl Itaconate Conjugate Modulates Inflammatory Response.

Itaconic acid and its derivative 4-octyl itaconate (OI) represent a novel anti-inflammatory medication that has demonstrated efficacy in multiple inflammation models because of its minimal side effects. Recently, natural polymers conjugated with small molecule drugs, known as polymer-drug conjugates (PDCs), have emerged as a promising approach to sustained drug release. In this work, we reported an approach to prepare a PDC containing an OI and make it into an injectable hydrogel. Chitosan (CS) was selected for PDC synthesis because of its abundant free amino groups that can be conjugated with molecules containing carboxyl groups by carbodiimide chemistry. We used an ethanol/water cosolvent system to synthesize a CS-OI conjugate via EDC/NHS catalysis. The CS-OI conjugate had improved water solubility and unique anti-inflammatory activity and did not show compromised antibacterial activity compared with unmodified CS. Beta-glycerophosphate (ß-GP) cross-linked CS-OI hydrogel exhibited good injectability with sustainable OI release and effectively modulated inflammatory response in a rat model. Therefore, this study provides valuable insights into the design of PDC hydrogels with inflammatory modulatory properties.

Overcoming Challenges of Incorporation of Biobased Dibutyl Itaconate in (Meth)acrylic Waterborne Polymers.

Polymeric derivatives of itaconic acid are gaining interest as biobased alternatives to petroleum-based monomers due to their versatility, renewable nature, commercial availability, and cost-effectiveness. Itaconate ester monomer's challenges incorporating in (meth)acrylic waterborne polymers are the low propagation rate, unfavorable reactivity ratios, and the depropagation process. To overcome these challenges, the seeded semibatch emulsion polymerization of 100% biobased dibutyl itaconate, methyl methacrylate, and butyl acrylate was investigated at different temperatures. Consequently, 30 wt % DBI was successfully incorporated within waterborne (meth)acrylates in short reaction times (4 h), obtaining high DBI incorporation (>90%). The results demonstrate that DBI incorporation influences the instantaneous monomer conversion, polymer's microstructure, and mechanical properties. By incorporating a biobased itaconate cross-linker, kinetics and mechanical characteristics of the polymers were improved. This combined approach can be implemented without altering industrial processes, resolving the commercialization dilemma for itaconate monomers to synthesize high-performance biobased polymers for adhesive and coating industries.

Computational Insights into SARS-CoV-2 Main Protease Mutations and Nirmatrelvir Efficacy: The Effects of P132H and P132H-A173V.

Nirmatrelvir, a pivotal component of the oral antiviral Paxlovid for COVID-19, targets the SARS-CoV-2 main protease (Mpro) as a covalent inhibitor. Here, we employed combined computational methods to explore how the prevalent Omicron variant mutation P132H, alone and in combination with A173V (P132H-A173V), affects nirmatrelvir's efficacy. Our findings suggest that P132H enhances the noncovalent binding affinity of Mpro for nirmatrelvir, whereas P132H-A173V diminishes it. Although both mutants catalyze the rate-limiting step more efficiently than the wild-type (WT) Mpro, P132H slows the overall rate of covalent bond formation, whereas P132H-A173V accelerates it. Comprehensive analysis of noncovalent and covalent contributions to the overall binding free energy of the covalent complex suggests that P132H likely enhances Mpro sensitivity to nirmatrelvir, while P132H-A173V may confer resistance. Per-residue decompositions of the binding and activation free energies pinpoint key residues that significantly affect the binding affinity and reaction rates, revealing how the mutations modulate these effects. The mutation-induced conformational perturbations alter drug-protein local contact intensities and the electrostatic preorganization of the protein, affecting noncovalent binding affinity and the stability of key reaction states, respectively. Our findings inform the mechanisms of nirmatrelvir resistance and sensitivity, facilitating improved drug design and the detection of resistant strains.

Struvite and ethylenediaminedisuccinic acid (EDDS) enhance electrokinetic-biological permeable reactive barrier removal of copper and lead from contaminated loess.

Removal of heavy metals using the electrokinetic (EK) remediation technology is restricted by soils containing a fraction of clay particles above 12%. Furthermore, it is also affected by hydroxide precipitation (focusing phenomenon) close to the cathode. A modified EK reactor containing a permeable reactive barrier (PRB) was proposed herein where the enzyme-induced carbonate precipitation (EICP) treatment was incorporated into the PRB. Despite that, NH4+-N pollution induced by the urea hydrolysis resulting from the EICP treatment causes serious threats to surrounding environments and human health. There were four types of tests applied to the present work, including CP, TS1, TS2, and TS3 tests. CP test neglected the bio-PRB, while TS1 test considered the bio-PRB. TS2 test based on TS1 test tackled NH4+-N pollution using the struvite precipitation technology. TS3 test based on TS2 test applied EDDS to enhance the removal of Cu and Pb. In CP test, the removal efficiency applied to Cu and Pb removals was as low as approximately 10%, presumably due to the focusing phenomenon. The removal efficiency was elevated to approximately 24% when the bio-PRB and the electrolyte reservoir were involved in TS1 test. TS2 test indicated that the rate of struvite precipitation was 40 times faster than the ureolysis rate, meaning that the struvite precipitate had sequestered NH4+ before it started threatening surrounding environments. The chelation between Cu2+ and EDDS took place when EDDS played a part in TS3 test. It made Cu2+ negatively surface charged by transforming Cu2+ into EDDSCu2-. The chelation caused those left in S4 and S4 to migrate toward the bio-PRB, whereas it also caused those left in S1 and S2 to migrate toward the anode. Due to this reason, the fraction of Cu2+ removed by the bio-PRB and the electrolyte reservoir is raised to 32% and 26% respectively, and the fraction of remaining Cu was reduced to 41%. Also, the removal efficiency applied to Pb removal was raised to 50%. Results demonstrate the potential of struvite and EDDS-assisted EK-PRB technology as a cleanup method for Cu- and Pb-contaminated loess.

Starch Sodium Octenylsuccinate as a New Type of Stabilizer in the Synthesis of Catalytically Active Gold Nanostructures.

Here, starch derivatives, i.e., sodium starch octenylsuccinate (OSA starch, hereinafter referred to as OSA), were employed as both reducing and stabilizing agents for the unique, inexpensive, and simple synthesis of gold nanoparticles (OSA-AuNPs) in an aqueous solution with gold salt. The obtained OSA-AuNPs were characterized by UV-vis spectrophotometry, transmission electron microscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The catalytic activity of the obtained gold colloids was studied in the reduction of organic dyes, including methylene blue (C.I. Basic Blue 9) and rhodamine B (C.I. Basic Violet 10), and food coloring, including tartrazine (E102) and azorubine (E122), by sodium borohydride. Moreover, OSA-AuNPs were utilized as signal amplifiers in surface-enhanced Raman spectroscopy. The obtained results confirmed that gold nanoparticles can be used as effective catalysts in reduction reactions of selected organic dyes, as well as signal enhancers in the SERS technique.

Pharmacokinetics and antioxidant activity of dihydrocaffeic acid grafted chitosan nanomicelles loaded with chicoric acid in broilers.

Chicoric acid (CA) is a natural nutrient found in plants, showcasing diverse biological activities, including anti-inflammatory and antioxidant properties. Despite its valuable properties, CA faces limitations in bioavailability and susceptibility to oxidative breakdown during utilization. Previous research introduced synthesized dihydrocaffeic acid grafted chitosan self-assembled nanomicelles (DA-g-CS), demonstrating its potential to enhance CA absorption. This study aims to investigate the pharmacokinetics, tissue distribution, and antioxidant activity of both CA and DA-g-CS loaded CA (DA-g-CS/CA) in broilers. An IPEC-J2 cell model was established and evaluated to delve deeper into the transport mechanism and antioxidant potential. The in vivo pharmacokinetic analysis in broilers highlighted a substantial difference: the maximum plasma concentration (Cmax) of DA-g-CS/CA exceeded CA by 2.6-fold, yielding a notable increased relative bioavailability to 214%. This evidence underscores the significant enhancement in CA's oral absorption, facilitated by DA-g-CS. The collective evaluation outcomes affirm the successful development of the cell model, indicating its suitability for drug transporter experiments. The findings from the intestinal transit analysis revealed that both CA and DA-g-CS/CA underwent passive entry into IPEC-J2 cells. Notably, the cellular uptake rate of DA-g-CS loaded with CA was significantly amplified, reaching 2.1 times higher than that of CA alone. Intracellular transport mechanisms involved microtubules, lysosomes, and the endoplasmic reticulum, with an additional pathway involving the endoplasmic reticulum observed specifically for DA-g-CS/CA, distinguishing it from CA. Moreover, the results from both in vivo and in vitro antioxidant assessments highlight the potent antioxidant activity of DA-g-CS/CA, showcasing its efficacy in preventing and treating cellular damage induced by oxidative stress. In summary, these findings underscore the significant enhancement of CA's efficacy facilitated by DA-g-CS, establishing a robust theoretical foundation for the prospective application of CA within livestock and poultry farming.

Structural and functional characterization of itaconyl-CoA hydratase and citramalyl-CoA lyase involved in itaconate metabolism of Pseudomonas aeruginosa.

Itaconate is a key anti-inflammatory/antibacterial metabolite in pathogen-macrophage interactions that induces adaptive changes in Pseudomonas aeruginosa-exposed airways. However, the impact and mechanisms underlying itaconate metabolism remain unclear. Our study reveals that itaconate significantly upregulates the expression of pyoverdine in P. aeruginosa and enhances its tolerance to tobramycin. Notably, the enzymes responsible for efficient itaconate metabolism, PaIch and PaCcl, play crucial roles in both utilizing itaconate and clearing its toxic metabolic intermediates. By using protein crystallography and molecular dynamics simulations analyses, we have elucidated the unique catalytic center and substrate-binding pocket of PaIch, which contribute to its highly efficient catalysis. Meanwhile, analysis of PaCcl has revealed how interactions between domains regulate the conformational changes of the active sites and binding pockets, influencing the catalytic process. Overall, our research uncovers the significance and mechanisms of PaIch and PaCcl in the efficient metabolism of itaconate by P. aeruginosa.

Composite System of Lauryl Glucoside and Lauryl Glycoside Sulfosuccinate: Properties and Applications in Vitamin E Nanoemulsions.

The synergistic effect of surfactant compounding on performance can be leveraged to enhance product application performance. An investigation of the surface tension and emulsification properties revealed the complex synergistic effect of the composite system comprising lauryl glucoside (LG) and lauryl glycoside sulfosuccinate (LG-SS). The composite system was used as an emulsifier for vitamin E (VE) emulsification. VE nanoemulsions with high VE content were successfully prepared. The nanoemulsion appears homogeneous and transparent and has an average size of approximately 200 nm. It has better temperature and centrifugal stability, an antioxidant capacity 2.89 times that of untreated VE, and is not easily oxidized and deactivated. In this study, we successfully constructed a complex system of LG and its derivatives and applied it to VE emulsification - this is a step toward expanding the effective application of glycosides and their derivative composite systems in food, pharmaceutics, and other industries.

High performance poly(L-lactic acid)-based film by one-step synthesis of poly (L-lactic acid-co-butylene itaconate-co-glycolic acid) for efficient preservation of yogurt storage.

Biodegradable poly(L-lactic acid) (PLLA) has seldom used for dairy packaging due to medium permeability and brittleness. Novel PLLA copolymers, poly (L-lactic acid-co-butylene itaconate-co-glycolic acid) (PLBIGA), were developed by integrating glycolic acid (GA) and poly(butylene itaconate) (PBI) into PLLA's structure using low molecular weight PLLA as a key initiator. Then, packaging materials with better barrier and mechanical properties were obtained by blended PLBIGA with PLLA. Both PLLA/PLBIGA films and polyethylene nylon composite film (PE/NY) were used for stirred yogurt packaging and storage at 4 °C for 25 days. Results revealed that yogurt packed by PLLA/PLBIGA films maintained stabler water-holding capacity, color, and viscosity over the storage period. Moreover, the integrity of the gel structure and the total viable count of lactic acid bacteria in yogurt packaged in PLLA/40-PLBIGA8 were also found to be superior to those in PE/NY packages, highlighting its eco-friendly advantages in dairy packaging.

Synthesis and characterization of pH-sensitive nanocarrier based chitosan-g-poly(itaconic acid) for ciprofloxacin delivery for anti-bacterial application.

This study aims to develop pH-sensitive and controlled release of ciprofloxacin from ciprofloxacin-loaded grafted chitosan-coated zinc oxide nanoparticles (Cip@Gchit/Zn-NPs) for the treatment of bacterial infections in the human colon. For this aim, first, the chitosan-g-poly(itaconic acid) [Chit-g-poly (Itac)] was synthesized via grafting of itaconic acid onto chitosan in the presence of cerium ammonium nitrate (CAN) under an inert atmosphere using conventional methods, while zinc oxide nanoparticles (Zn-NPs) were prepared via sol-gel technique. Characterization of the synthesized Cip@Gchit/Zn-NPs was analyzed using XRD, FT-IR, SEM, TGA, and zeta potential analysis. The antibacterial efficacy of Cip@Gchit/Zn-NPs against three pathogenic bacteria, namely Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, was superior to that of tetracycline reference drugs, as evidenced by larger inhibition zones. Cytotoxicity assessment of Cip@Gchit/Zn-NPs on the human chondrocyte cell line C28/I2 via MTT assay revealed 100 % cell viability at a concentration of 500 µg/mL. The loading efficiency of ciprofloxacin into Gchit/Zn-NPs was evaluated at various ratios, demonstrating lower loading efficiency; however, sustained release of ciprofloxacin from Cip@Gchit/Zn-NPs was excellent, with 98.13 % release observed at pH 7.2 over 10 h. Kinetic analysis of ciprofloxacin release followed the first-order kinetic models.

Structural and functional insights of itaconyl-CoA hydratase from Pseudomonas aeruginosa highlight a novel N-terminal hotdog fold.

Itaconyl-CoA hydratase in Pseudomonas aeruginosa (PaIch) converts itaconyl-CoA to (S)-citramalyl-CoA upon addition of a water molecule, a part of an itaconate catabolic pathway in virulent organisms required for their survival in humans host cells. Crystal structure analysis of PaIch showed that a unique N-terminal hotdog fold containing a 4-residue short helical segment α3-, named as an "eaten sausage", followed by a flexible loop region slipped away from the conserved ß-sheet scaffold, whereas the C-terminal hotdog fold is similar to all MaoC. A conserved hydratase motif with catalytic residues provides mechanistic insights into catalysis, and existence of a longer substrate binding tunnel may suggest the binding of longer CoA derivatives.

Effects of folate-chicory acid liposome on macrophage polarization and TLR4/NF-κB signaling pathway in ulcerative colitis mouse.

BACKGROUND: Chichoric acid (CA) is a major active ingredient found in chicory and Echinacea. As a derivative of caffeic acid, it has various pharmacological effects. PURPOSE: Due to the unclear etiology and disease mechanisms, effective treatment methods for ulcerative colitis (UC) are currently lacking. The study investigated the therapeutic effects of the folate-chicory acid liposome on both LPS-induced macrophage inflammation models and dextran sulfate sodium (DSS)-induced mouse UC models. METHODS: Folate-chicory acid liposome was prepared using the double emulsion ultrasonic method with the aim of targeting folate receptors specifically expressed on macrophages. The study investigated the therapeutic effects of the folate-chicory acid liposome on both LPS-induced macrophage inflammation models and DSS -induced mouse UC models. Furthermore, the effects of the liposomes on macrophage polarization and their underlying mechanisms in UC were explored. RESULTS: The average particle size of folate-chicory acid liposome was 120.4 ± 0.46 nm, with an encapsulation efficiency of 77.32 ± 3.19 %. The folate-chicory acid liposome could alleviate macrophage apoptosis induced by LPS, decrease the expression of inflammatory factors in macrophages, enhance the expression of anti-inflammatory factors, inhibit macrophage polarization towards the M1 phenotype, and mitigate cellular inflammation in vetro. In vivo test, folate-chicory acid liposome could attenuate clinical symptoms, increased colon length, reduced DAI scores, CMDI scores, and alleviated the severity of colonic histopathological damage in UC mice. Furthermore, it inhibited the polarization of macrophages towards the M1 phenotype in the colon and downregulated the TLR4/NF-κB signaling pathway, thereby ameliorating UC in mice. CONCLUSION: Folate-chicory acid liposome exhibited a uniform particle size distribution and high encapsulation efficiency. It effectively treated UC mice by inhibiting the polarization of macrophages towards the M1 phenotype in the colon and downregulating the TLR4/NF-κB signaling pathway.

Fabrication of D-α-tocopheryl polyethylene glycol 1000 succinates and human serum albumin conjugated chitosan nanoparticles of bosutinib for colon targeting application; in vitro-in vivo investigation.

For more effective chemotherapy and targeted treatment of colorectal cancer, this study seeks to develop chitosan (CH)-human serum albumin (HAS)-D-α-tocopheryl polyethylene glycol 1000 (TPGS) nanoparticles (BOS-CH-HSA-TPGS-NPs) coated with Bosutinib (BOS). Nuclear magnetic resonance (NMR) indicated that chitosan's structure was modified by carbodiimide coupling with HSA. We used a Box-Behnken design to find the ideal region for particle size, zeta potential, and entrapment efficiency, eventually emerging at a formulation with these values: 187.14 ± 3.2 nm, 76.2 ± 0.96 %, and 21.1 ± 2.3 mV. Differential scanning calorimetry (DSC), Transmission electron microscopy (TEM), X-ray diffraction (XRD), Atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), High-performance liquid chromatography (HPLC) were all used to characterize the sample in detail. At a phosphate buffer pH of 7.4, in vitro drug release tests showed both Higuchi model release (0.954) and Fickian diffusion (n = 0.5). Compared to free BOS, HCT116 cell lines showed considerably higher cytotoxicity in in vitro cytotoxicity assays. In male albino Wistar rats, the BOS-CH-HSA-TPGS-NPs also showed enhanced pharmacokinetics, targeting efficiency, and biocompatibility. When used to the treatment of colorectal cancer, the BOS-CH-HSA-TPGS NPs show promise as a sustained-release therapy with improved therapeutic effects by addressing the challenges of poor solubility, poor permeability, and toxic side effects.

Development of poly(butylene adipate-co-butylene succinate-co-ethylene adipate-co-ethylene succinate) (PBEAS) net twine as biodegradable fishing gear.

Nylon fishing nets have excellent strength and durability, but when lost at sea, their insufficient decomposition destroys habitats and spawning grounds, and pollutes the marine environment. This led to the development of poly(butylene succinate) (PBS) resin for biodegradable fishing gear based on aliphatic fibers. Prompted by the low stiffness and elastic recovery of PBS, we introduced two additional components into the molecular structure of PBS: adipic acid and ethylene glycol. These two new components were combined with succinic acid and 1,4-butanediol, the existing components of PBS, to synthesize poly(butylene adipate-co-butylene succinate-co-ethylene adipate-co-ethylene succinate) (PBEAS) resin via esterification and polycondensation reactions of a quaternary aliphatic copolyester. Although the molecular weight and molecular weight distribution of PBEAS are similar to those of PBS, it has excellent tensile strength, stiffness, elastic recovery, and biodegradability, with a low melting point for good production efficiency. These improvements are expected to allow PBEAS resin to be applied to gill nets for fish that require high stiffness, thereby expanding the use of biodegradable fishing gear.

Discovery of Itaconate-Mediated Lysine Acylation.

Itaconate is an important antimicrobial and immunoregulatory metabolite involved in host-pathogen interactions. A key mechanistic action of itaconate is through the covalent modification of cysteine residues via Michael addition, resulting in "itaconation". However, it is unclear whether itaconate has other regulatory mechanisms. In this work, we discovered a novel type of post-translational modification by promiscuous antibody enrichment and data analysis with the open-search strategy and further confirmed it as the lysine "itaconylation". We showed that itaconylation and its precursor metabolite itaconyl-CoA undergo significant upregulation upon lipopolysaccharides (LPS) stimulation in RAW264.7 macrophages. Quantitative proteomics identified itaconylation sites in multiple functional proteins, including glycolytic enzymes and histones, some of which were confirmed by synthetic peptide standards. The discovery of lysine itaconylation opens up new areas for studying how itaconate participates in immunoregulation via protein post-translational modification.